Substantial evidence from Iaboratory studies has indicated an important role of reactive oxygen species (ROS), produced by estrogen metabolism, in mammary carcinogenesis. This application is to evaluate whether the biomarker of systemic oxidative stress may be associated with breast cancer risk, whether antioxidant polyphenols, consumed in large quantities among Chinese women in Shanghai, may reduce the risk of breast cancer, particularly among those with a high exposure to ROS. To achieve these research goals, we propose to conduct a nested case-control study of 430 breast cancer cases and 860 individually matched controls within the cohort of the Shanghai Women's Health Study (RO1CA 70867), a population-based cohort study of approximately 75,000 Chinese women. In addition to in-person interviews, blood (or buccal cell) and urine samples were collected from 87.5% cohort members. For this proposed study, urinary level of total phenols will be assayed with Folin-Ciocalteu Phenol Reagent, urinary levels of polyphenol flavonols and flavanols will be determined using liquid chromatography photo-diode array electrospray mass spectrometry, urinary level of 2,3-dinor-5,6-dihydro-15-F2t-lsoP will be quantified by gas chromatography/negative ion chemical ionization mass spectrometry, blood levels of tocopherols and carotenoids will be analyzed using HPLC methods, and genotypes of the enzymes involved in ROS detoxification will be assayed using PCR-RFLP methods. The associations between these biomarkers and breast cancer risk will be evaluated. We also will perform statistical analyses to evaluate the joint effects or potential interactions of total phenols, flavonols and flavanols with soy isoflavonoids, antioxidant nutrients, genotypes of ROS detoxification enzymes and oxidative stress level in relation to breast cancer risk. The study population will be unique given the high intake levels of total phenols, flavonols, flavanols, isoflavonoids. Because questionnaire data and specimen collection, follow-up survey as well as assays for isoflavonoids are supported by the existing study, this project will be very cost-efficient. In addition, we will also be able to expand our study to a larger scale if the results are promising. Findings from this study will have important public health implications in the primary prevention of breast cancer. [unreadable] [unreadable] [unreadable]